P1308: RUXOLITINIB AS GRAFT-VERSUS-HOST DISEASE PROPHYLAXIS FOR ALLOGENEIC STEM CELL TRANSPLANTATION IN APLASTIC ANEMIA PATIENTS
Authors: Xiaoyu Zhang, Jialin Wei, Yi He, Sizhou Feng, Mingzhe Han, Erlie Jiang
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) offers rapid hematopoietic reconstitution and long-term wellness for aplastic anemia (AA). However, high incidence of acute graft versus host disease (aGVHD) contributed to high treatment-related mortality (TRM). Since AA is a nonmalignant disorder, avoiding aGVHD remains a clinical concern. It has been well documented about the efficacy and safety of ruxolitinib in aGVHD. Aims: Our study aimed to determine the prophylactic value of ruxolitinib for aGVHD in HSCT recipients of AA. Methods: Between August 2021 and December 2022, 26 aplastic anemia patients applied for allo-HSCT were prospectively enrolled in this study at Institute of Hematology and Blood Diseases Hospital, CAMS and PUMC. Patients with HSCT were conditioned including FAC or BFAC regimen. The FAC conditioning regimen was composed of fludarabine (30 mg/m2/d, days -5 to -1), cyclophosphamide (37.5mg/kg/d, days -5 to -2), and rATG (2.5 mg/kg/d, days -5 to -1) or pALG (20 mg/kg/d, days -5 to -1). The BFAC conditioning regimen included busulfan (3.2mg/kg/d, days -7 to -6) on the basis of FAC. All recipients received cyclosporine A or tacrolimus, short-term methotrexate as GVHD prophylaxis. Besides, haplo-identical donor (HID)-HSCT recipients received mycophenolate mofetil consistent with the previous experience. Ruxolitinib was initiated at 5 twice daily until 3 months post-transplantation. Results: This study included 26 AA patients (median age: 32, ranging from 12 to 57) who were diagnosed very severe/severe AA (VSAA/SAA) (n=19), non-severe AA (n=5) and hepatitis-associated aplastic anemia (HAAA) (n=2). The donor type was a matched sibling donor (MSD) in 14 patients and a haploidentical related donor (HID) in 12 patients. With the application of ruxolitinib as prophylaxis, neutrophil and platelet engraftment took a median time of 14.5 (10 – 24) days and 26 (13 – 48) days, respectively, without graft failures (GF) cases observed. Acute GVHD developed in 4/26 patients, including 2 cases of Ⅲ to Ⅳ aGVHD. The 100-day cumulative incidence of severe aGVHD was 3.8±3.77%. In MSD-HSCT group, the incidence of grade II aGVHD was 7.69±7.39%, and no severe aGVHD incidence was documented. HID-HSCT group demonstrated higher cumulative incidence of grade II to Ⅳ aGVHD of 25±12.5% (95%CI 0.000~0.459), and grade Ⅳ aGVHD of 8.33±7.98% (95%CI 0.00~0.227). Three patients developed moderate chronic GVHD (cGVHD) after tapering or stopping ruxolitinib, with the incidence of cGVHD of 11.54%. CMV reactivation developed in 11 patients, and none were diagnosed CMV disease. Epstein-Barr Virus (EBV) infections developed in 2 patients and none of them developed EBV-associated posttransplant lymphoproliferative disorders (PTLD). After a median follow-up of 292 days (95%CI 215.333 to 368.664 days), only one patient in HID-HSCT died of severe sepsis and multi-organ dysfunction. The 2-year overall survival (OS) demonstrated at 95.5 ± 4.5% (95% CI, 0.871~1) at the whole cohort, 100% in the MSD-HSCT group, and 90.9 ± 8.7% (95% CI, 0.754~1) in the HID-HSCT group. Summary/Conclusion: This is the first study investigating the prophylactic application of ruxolitinib for aplastic anemia patients after allo-HSCT. Ruxolitinib would be a promising and safe choice in preventing aGVHD, but this awaits further study in larger cohorts.Keywords: Acute graft-versus-host disease, Allogeneic hematopoietic stem cell transplant, Aplastic anemia